Bacterial toxins have been known to be primary mediators of a number of diseases both of the intestinal tract and of other organ systems. Some bacterial toxins are known as AB-type toxins, since they are composed of a catalytic A subunit and a cell-binding B subunit. Examples of such AB-type toxins include cholera toxin (CT), the E. coli heat-labile toxin (LT) responsible for traveler's diarrhea, the B. pertussis toxin responsible for much of the symptomatology of whooping cough, exotoxin-A produced by Pseudomonas aeruginosa strains often found in the respiratory tract of cystic fibrosis patients or on the damaged skin of burn patients, Shiga toxin produced in the intestinal disease shigellosis, and the similar toxin produced by enterohemorrhagic E. coli and which has lately been associated in the U.S. with contaminated produce and ground beef products.
Typically, the diseases caused by these bacterial toxins are treated symptomatically because drugs effective against the toxins themselves have not been available. Except in the case of pertussis, prior immunizations have either not been available or have not been very successful in conferring a protective immunity against these toxins.
Accordingly, there is a great need for drugs that would act directly against these toxins, interfering with their mechanisms of action so as to prevent entry of the active toxin into targeted host cells and cellular intoxication. The present invention provides such long-needed drugs and discloses a proposed new model mechanism by which extracellular AB-type toxins gain access to the affected cells of the body.